This is an educational talk about the treatment of organophosphorus poisoning (OP) based upon a talk given at the Australasian college of Emergency Medicine, Annual scientific sessions Nov 2010, canberra. If you liked this presentation; please also check out this page created by one of my senior colleagues (and watch the video) :- http://curriculum.toxicology.wikispaces.net/2.2.7.4.5+Organophosphates
Organophosphate Poisoning Treatment - port headland doctor teaching (31-1-12)
1. Current concepts and
controversies in OP
management
Dr Bishan Rajapakse
PhD Candidate Australia National University,
Emergency Medicine Registrar, Sydney
South Asian Clinical Toxicology Research Collaboration
(SACTRC)
Abbreviated version of talk from -ACEM
21st -25th November 2010, Canberra
Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)
2. PhD - “Improving the emergency management
of OP poisoning through research and medical
education ” (2006-2010)
• Advanced Trainee
– Wellington NZ 2005 (1st year Ad Tr)
– Sydney Oz, Aug 2010 – April 2011
– Locuming June 2010 onwards until
PhD submitted
• South Asian Clinical Toxicology
Research Collaboration (SACTRC)
– Research collaboration
– 5 Hospitals in Sri Lanka
• PhD Topics
– Use of biomarkers in OP
poisoning (RBC-AChE)
– Rural doctor resuscitation
education
Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)
3. Management of OP poisoning is
Important in Emergency Medicine!
• Prevalent in developing
world
– 200,000 deaths /year
– Self–poisoning
predominates
• 15-30% mortality
– (0.3% for all poisoning in
the west)
• Also affects developed
world nations
– Occupational exposure &
HAZMAT incidents
– Nerve gas attacks
Eddleston M, Buckley NA, Eyer P, Dawson AH. Management of acute organophosphorus pesticide poisoning.
Lancet. Feb 16 2008;371(9612):597-607.
Dr can we learn from - OP Update sarin attacks? Przegl st2012)
Vale A. What lessons Bishan Rajapakse the Japanese (Port Hedland Jan 31 Lek. 2005;62(6):528-532.
4. PhD Paradox
“The only thing I know is
that I don’t know anything”
- Socrates
Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)
8. Convenient: Source of Poison
Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)
9. Alcohol
Use of alcohol during self-harm
in Uda Walawe
Men
68%
Women
?
Konradsen et al, 2004
Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)
10. High mortality & morbidity in
pesticide poisoning is Multi-factorial
• High toxicity of agents (15-30%
mortality in OPs)
– Lack of 100% effective antidote for the
biggest killers
Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)
12. Dangerous GI decontamination
• “Iatrogenic”
component of
mortality &
morbidity
• 14 consecutive
OP poisonings
– 7 Aspiration
Pneumonia
– 2 Deaths
Images courtesy of Dr Michael Eddleston
The Hazards of Gastric Lavage for Intentional Self-Poisoning in a
Dr Poor LocationClinTox Hedland Jan 31st2012)
ResourceBishan Rajapakse - OP Update (Port2007;45(2):136-43
14. Mechanism - Inhibition of
Acetycholinesterase
Dr Bishan Rajapakse - OP UpdateCNSForum.com 31st2012)
Image accessed from (Port Hedland Jan
15. Mechanism - Inhibition of
Acetycholinesterase
Figure from Chapter: “Organophosphorus and Carbamate Agents (Anti-cholinesterase pesticide poisoning)” –
st
B.Rajapakse, N. Buckley - Dr Bishan Rajapakse - OPTextbook” Ed S David, WoltersKluwer (In press)
“Emergency Medicine Update (Port Hedland Jan 31 2012)
16. OP Poisoning –
Complex Multi-system presentation
Life threatening
Cholinergic
Effects on features
Neuro: GCS
Central - Seizure
(CNS)
Resp:
Lung
Secretions
- Respiratory muscle weakness
P
Autonomic
Peripheral S CVS: HR
(PNS) BP
Somatic
+ Death
Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)
17. OP Poisoning –
Complex Multi-system presentation
Life threatening
Cholinergic
Effects on features
Neuro: GCS
Central - Seizure
(CNS)
Resp:
Lung
Secretions
- Respiratory muscle weakness
P
Autonomic
Peripheral S CVS: HR
(PNS) BP
Somatic
+ Death
Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)
18. Clinical cases
Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)
19. CASE
0900 hrs • Drunk 100mls after
(village) dispute
36 yo female
0930 hrs • Found by family
Ingestion of
vomiting
Dimethoate
(Severely Toxic OP) 1000 hrs • Taken to nearest
Village peripheral hospital
(1 doctor, 2 nurses)
• Sent by Ambulance
1115 hrs (no paramedics) to
nearest General
hospital
Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)
20. Spectrum of disease
• Acute cholinergic syndrome
– Immediate onset
• Intermediate Syndrome
– Delayed respiratory failure (24-96hrs)
– Nerve conduction can predict weakness
• OP induced delayed peripheral
neuropathy
Jayawardane P, Dawson AH, Weerasinghe V, Karalliedde L, Buckley NA, Senanayake N. The
spectrum of intermediate syndrome following acute organophosphate poisoning: a prospective
cohort study from Sri Lanka.Rajapakse - OP Update (Port Hedland Jan 31st2012)
Dr Bishan PLoS Med. Jul 15 2008;5(7):e147.
21. OP poison Management
• Resuscitation!
– A, B, C, D
– Consider early intubation
• IV Atropine
– Stops lung secretions
– Increases blood pressure
Eddleston M, Buckley NA, Eyer P, Dawson AH. Management of
acute organophosphorus pesticide poisoning. Lancet. Feb 16
2008;371(9612):597-607. - OP Update (Port Hedland Jan 31st2012)
Dr Bishan Rajapakse
22. End points of atropinisation
Lung Secretions Clear Chest
A
Hypotension
T sBP > 80mmHg
R
Bradycardia
O HR > 80/min
P
Sweating
I Dry Axillae
N
E (Pupils no longer
(Miosis)
pinpoint)
Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)
23. Atropine - Doubling Dose regime
• Large doses of Atropine are required
– Mean dose in severe OP poisoning 23.4mg (range 1-
75mg)
• Text book recommendations vary
– Upto 1,380 minutes to administer 23.4mg
• Doubling IV bolus doses most effective
– Eg. 2mg, then 4mg, then 8mg etc every 5 minutes
until “clinical response”
– Continue with 10-20% of loading dose/hour
Eddleston et al. Speed of initial atropinisation in significant organophosphorus pesticide
poisoning--a systematic comparison of recommended regimens. J.Toxicol.Clin.Toxicol.
2004;42(6):865-75.
Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)
24. Antidotes in OP poisoning Rx
• Acute Cholinergic Syndrome:
ATROPINE
A
• Neuro: Low GCS, Coma, Seizure
B
• Resp: Lung Secretions
C
Respiratory Muscle Weakness
D
• CVS: Bradycardia and Hypotension
DIAZEPAM
Oximereactivators
Roberts DM, Aaron CK. Management of acute organophosphorus pesticide
st2012)
poisoning. Bmj. Mar Bishan Rajapakse - OP Update (Port Hedland Jan 31
Dr
24 2007;334(7594):629-634.
25. Oxime RCT – concluding
statements
• No evidence for benefit (WHO dose
regime of Pralidoxime)
• Reasons for failure were not apparent
• Further studies needed
– Different dose regimes (OP specific)
– Different Oximes
Eddleston M, Eyer P, Worek F, et al. Pralidoxime in acute organophosphorus insecticide
poisoning--a randomised controlled trial. PLoS Med. Jun 30 2009;6(6):e1000104.
Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)
26. But would you give Oximes?
Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)
27. Practicing Evidence Based
Medicine
Three factors:
–The Evidence
–Clinical Expertise
–The Patient
Source: Discussion with Prof Tony Celenza - UWA
Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)
28. Oxime Summary
How would I treat a symptomatic OP pt?
• Patient responding to atropine - would
use this alone and not use pralidoxime.
• If they are not getting better or
decompensating with atropine, then treat
with pralidoxime
Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)
29. Discussion:
…..Time for your thoughts!
Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)
30. Conclusions
• Pesticide poisoning large global public
health problem
• Treatment of OP poisoning = Atropine (++)
& Resuscitation (Simultaneously)
• Endpoints of atropinisation; BP, P,
Lung secretions, secretions
• Oxime therapy is controversial – use if not
improving with atropine
Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)
31. Acknowledgements – Thanks!
SACTRC
I would like to acknowledge all
the staff at the South Asian clinical toxicology
research collaboration, and in particular:-
Professor Nick Buckley, Professor Andrew Dawson, Dr Indika
Gawarmanna, Dr Michael Eddleston, Dr Darren Roberts & Mr Lalith
Senarathna
Sri Lanka Hospital Staff
I would like to thank and acknowledge the patients and the hospital
staff of Sri Lankan hospitals for their support in my research
New Zealand Emergency Physicians
Dr Paul Quigley, Dr Craig Wallace, Dr Sandra Rattenbury
Funders & University
Welcome Trust (GR071669) & Australia National University
Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)
32. “Imagination is more
important than knowledge”
Albert Einstein
Dr Bishan Rajapakse - OP Update (Port Hedland Jan 31st2012)
Hinweis der Redaktion
It’s the same in medicine – we just keep finding out how much we thought was correct perhaps isnt, and how much we don’t really know, the only difference is that as we get qualificaitons we are more confident about saying what we don’t know!
The most common group are OP and one of the most deadly, next to paraquat which is also seen in high numbers.
EASY ACCCESS
The other important
Also worthy of mention when considering why the Mortality and morbidity is high is the Iatrogenic componentForced emesis and gastric lavage were we accepted practice of poison management world world wide many decades ago, but during the last 3 decades in the west the was the realisation that forced emesis was a dangerous practice, and the benefits of even Gastric lavage which is slightly more controlled is still limited, and still dangerous if there is a decreased level of consciousness when performed in a non intubated patient. However, despite this there is still the widespread practice of both these procedures throughout asia, and this early reserch by Michael eddleston conducted in Sri Lanka documented that in 14 consecutive OP poisonings that there were 7 cases of aspiration pneumonia and 2 deaths related to this. This gives an idea of the magnitude of a potentially iatrogenic component to the high mortality and morbidity – this also suggests the importance of both good education in poisoning management and also the importance of resuscitation education. Knowledge / practice GapDangerous GI decontamination despite established poison treatment protocolsIneffective resuscitation practice and trainingAnother factor is the dangerous decontamination practices – such as the widespread use of forced emesis – which involves often the patient drinking 3 litres of bicarbonate until they vomit. Also other practices include using a widebore orogastric tubes or nasogastric tubes in patients with low leves of consciousness who are not intubated. One study looked at 14 consetcutive patients with OP poisong where there was an incidence of aspiration pneumonia in 7 and death in 2.
We performed a double-blind randomised placebo-controlled trial of pralidoxime chloride (2 g loading dose over 20 min, followed by a constant infusion of 0.5 g/h for up to 7 d) versus saline in patients with organophosphorus insecticide self-poisoningTwo hundred thirty-five patients were randomised to receive pralidoxime (121) or saline placebo (114). N=235CONCLUSIONS: Despite clear reactivation of red cell acetylcholinesterase in diethyl organophosphorus pesticide poisoned patients, we found no evidence that this regimen improves survival or reduces need for intubation in patients with organophosphorus insecticide poisoning. The reason for this failure to benefit patients was not apparent. Further studies of different dose regimens or different oximes are required.